Morphological features of synaptic structures associated with amyloid plaques in the human cerebral cortex

Abstract

BACKGROUND: Synapse damage and loss are fundamental to the pathogenesis of Alzheimer’s disease (AD) and lead to reduced cognitive function. Therefore, the study of synaptic abnormalities is crucial for understanding the pathogenesis and progression of AD. Synaptophysin, a transmembrane protein of synaptic vesicles, is most widely used as an immunohistochemical marker of synapses. AIM: to study the morphological features of synaptophysin–containing elements in the human cerebral cortex with amyloid plaques. METHODS: This study was made on the cerebral cortex samples of men and women aged 65 to 94 years (n = 10). Synapses and amyloid plaques were simultaneously detected with a new original light microscopy technique. This technique is based on immunohistochemical staining for synaptophysin and histochemical staining of amyloid plaques with Alcian blue. RESULTS: Abnormal synaptophysin-immunopositive structures presumed to be dystrophic presynapses were found within most of the identified amyloid plaques. These structures have large sizes and indistinct shapes and are present exclusively within amyloid plaques. Interestingly, corpora amylacea were also identified in all samples. They have spherical shapes and are located mainly in the perivascular, periventricular, and subpial regions of the brain. In all analyzed samples, synaptophysin-immunopositive terminals surrounding corpora amylacea had normal morphology and density and showed no signs of pathology. CONCLUSION: In this work, abnormal synaptophysin-containing structures associated with amyloid plaques were found in the human cerebral cortex using the original staining technique. Further study of these structures holds promise for identifying new biomarkers of synaptic disorganization, including in Alzheimer's disease.